help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on August 18, 2004, doi:10.1164/rccm.200312-1668OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 10, November 2004, 1101-1107

A more recent version of this article appeared on November 15, 2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200312-1668OCv1
170/10/1101    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kunichika, N.
Right arrow Articles by Yuan, J. X-J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kunichika, N.
Right arrow Articles by Yuan, J. X-J

Submitted on December 8, 2003
Accepted on August 16, 2004

Bosentan Inhibits Transient Receptor Potential Channel Expression in Pulmonary Vascular Myocytes

Naomi Kunichika1, Judd W Landsberg1, Ying Yu1, Hideki Kunichika1, Patricia A Thistlethwaite1, Lewis J Rubin1, and Jason X-J Yuan1*

1 Departments of Medicine and Surgery, University of California, San Diego, La Jolla, CA, USA

* To whom correspondence should be addressed. E-mail: xiyuan{at}ucsd.edu.

Bosentan, a dual endothelin receptor blocker, has been used clinically to treat idiopathic pulmonary arterial hypertension (IPAH). However, the mechanism of its antiproliferative effect on pulmonary artery smooth muscle cells (PASMC) remains unclear. A rise in cytoplasmic Ca2+ stimulates PASMC proliferation, and the canonical transient receptor potential (TRPC) channels are an important pathway for Ca2+ entry during PASMC proliferation. Bosentan (20-50 µM) significantly inhibited endothelin-1- or platelet-derived growth factor (PDGF)-mediated PASMC growth and 3H-thymidine uptake. In PASMC, endothelin-1 (1 µM) and PDGF (10 ng/ml) both upregulated protein expression of TRPC6, whereas bosentan markedly downregulated TRPC6 protein levels. Furthermore, TRPC6 expression in PASMC from IPAH patients was greater than in normal PASMC, and the antiproliferative effect of bosentan was significantly enhanced in IPAH-PASMC in comparison to normal PASMC. These observations demonstrate that the antiproliferative effect of bosentan on PASMC involves the downregulation of TRPC6 channels via a mechanism possibly independent of endothelin receptor blockade. The greater effect of bosentan on IPAH-PASMC than on normal PASMC suggest that increased TRPC6 expression and function may be involved in the overgrowth of PASMC in IPAH patients.
Key words: endothelin-1, Ca2+ channels, transient receptor potential cation channels




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
K. Smedlund and G. Vazquez
Involvement of Native TRPC3 Proteins in ATP-Dependent Expression of VCAM-1 and Monocyte Adherence in Coronary Artery Endothelial Cells
Arterioscler. Thromb. Vasc. Biol., November 1, 2008; 28(11): 2049 - 2055.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. Lu, J. Wang, L. A. Shimoda, and J. T. Sylvester
Differences in STIM1 and TRPC expression in proximal and distal pulmonary arterial smooth muscle are associated with differences in Ca2+ responses to hypoxia
Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L104 - L113.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Nishida, N. Onohara, Y. Sato, R. Suda, M. Ogushi, S. Tanabe, R. Inoue, Y. Mori, and H. Kurose
G{alpha}12/13-mediated Up-regulation of TRPC6 Negatively Regulates Endothelin-1-induced Cardiac Myofibroblast Formation and Collagen Synthesis through Nuclear Factor of Activated T Cells Activation
J. Biol. Chem., August 10, 2007; 282(32): 23117 - 23128.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
B. Nilius, G. Owsianik, T. Voets, and J. A. Peters
Transient Receptor Potential Cation Channels in Disease
Physiol Rev, January 1, 2007; 87(1): 165 - 217.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. W. Bush, D. B. Hood, P. J. Papst, J. A. Chapo, W. Minobe, M. R. Bristow, E. N. Olson, and T. A. McKinsey
Canonical Transient Receptor Potential Channels Promote Cardiomyocyte Hypertrophy through Activation of Calcineurin Signaling
J. Biol. Chem., November 3, 2006; 281(44): 33487 - 33496.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
R. Inoue, L. J. Jensen, J. Shi, H. Morita, M. Nishida, A. Honda, and Y. Ito
Transient Receptor Potential Channels in Cardiovascular Function and Disease
Circ. Res., July 21, 2006; 99(2): 119 - 131.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. F. Alvarez, J. A. King, and M. I. Townsley
Resistance to Store Depletion-induced Endothelial Injury in Rat Lung after Chronic Heart Failure
Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1153 - 1160.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
B. Nilius, T. Voets, and J. Peters
TRP Channels in Disease
Sci. Signal., August 2, 2005; 2005(295): re8 - re8.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
T. D. Bradley, Y. E. Miller, F. J. Martinez, D. C. Angus, W. MacNee, and E. Abraham
Interstitial Lung Disease, Lung Cancer, Lung Transplantation, Pulmonary Vascular Disorders, and Sleep-disordered Breathing in AJRCCM in 2004
Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 675 - 685.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2004 American Thoracic Society 		  ATS State of the Art 2009